Plants and plant extracts have been used for centuries for medicinal purposes, and bio-prospecting continues in modern times. Identification and characterization of an individual therapeutic property and the responsible compound is a resource-intensive and unpredictable system, but it is vital in the on-going search for therapeutic agents to ameliorate diseases and other detrimental health conditions.
Thionins generally are a class of small and very stable proteins produced by plants, and characterized by containing multiple di-sulfide bridges (usually three or four), being largely basic, and sharing substantial sequence homology. In addition to the European mistletoe viscotoxins, other thionins include phorotoxin, isolated from American mistletoe; purothionins, isolated from wheat: hordothionins, isolated from barley; a venothionin, isolated from rye; and crambin, isolated from cabbage.
Because of their broad distribution among plants, and because of their highly conserved amino acid sequence and structure, thionins may have an important purpose in plants. Thionins isolated from seeds have been speculated to play a role as storage proteins or toxins that protect the seeds from insect, bacterial or fungal invasion. Thionins isolated from leaves also are speculated to serve as toxins. Thionins isolated from barley leaf cells are known to be toxic to certain fungi, and barley plants exposed to spores of such fungi show a rapid increase in transcription levels of the leaf specific thionins.
Pyrularia thionin (PT) is a small, strongly basic 47 amino acid peptide produced by the parasitic plant Pyrularia pubera. The four disulfide bridges and amino acid sequence of PT place it in the thionin protein family (see FIG. 1). The amino acid sequences of Pyrularia thionin, of other thionins, and of related peptides are set forth in FIG. 1. Characterization of the biological properties of Pyrularia thionin has been underway for several years, and the toxic properties of this protein have been reported (see, e.g., Vernon et al., Arch. Biochein. Biophys. 238:18-29, 1985; Evett et al., Toxicon 24:622-625, 1986; and Gasanov et al., Cancer. Immunol. Immunother. 41:122-128, 1995).